What is bmp4

Antibodies Assays Proteins Inhib. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homo See more Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including neurogenesis, vascular development, angiogenesis and osteogenesis PubMed Additional gene information for BMP4 Gene.

Promoters and enhancers for BMP4 Gene. Interacts with GREM2. Predicted three dimensional structure from AlphaFold P Abcam antibodies for BMP4. Biorbyt antibodies for BMP4. Protein products for research BioLegend. Novus Biologicals proteins and lysates for BMP4. Abcam proteins for BMP4. Browse Sino Biological Assays. Family: Belongs to the TGF-beta family. Epiblast Cells Epiblast. Extraembryonic Ectoderm Cells Extraembryonic Ectoderm.

Intraembryonic Ectoderm Cells Ectoderm. Loose Mesenchyme Cells Metanephric Mesenchyme. Semilunar Valve Cells Semilunar Valves. Common Preadipocyte Lateral Plate Mesoderm. Dental Placode Cells Dental Placode. Lens Placode Cells Lens Placode. Surface Ectoderm Cells Surface Ectoderm. Ureter Cells Ureter.

Beta-like cells. Early mesoderm cells Mesoderm embryoid bodies Mesodermal embryoid bodies Mesoderm-like cells. Posterior primitive streak cells Primitive Streak Mesendoderm cells Primitive streak-like cells. Endoderm-like cells. Hematopoietic progenitor cells Mixed hematopoietic progenitor cells.

Select a section on the left to see content. Genes Dev. PLoS Biol. Short name:. Alternative name s :. Bone morphogenetic protein 2B Short name:. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues anophthalmia.

Disease description A birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. Once cleaved, a propeptide generally has no independent biological function. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.

Present also in normal and neoplastic prostate tissues, and prostate cancer cell lines. Interacts with GREM2. P With Exp. The information is filed in different subsections.

Length: Mass Da : 46, It is useful for tracking sequence updates. The algorithm is described in the ISO standard. Tissue Int. Full view. These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary citable accession number'.

See complete history. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Do not show this banner again. Cytokine , Developmental protein , Growth factor. Chondrogenesis , Differentiation , Osteogenesis.

Pathway Commons web resource for biological pathway data More PathwayCommons i. Reactome - a knowledgebase of biological pathways and processes More Reactome i. SignaLink: a signaling pathway resource with multi-layered regulatory networks More SignaLink i.

Homo sapiens Human. This is known as the 'taxonomic identifier' or 'taxid'. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.

We then explored whether the observed increase in recurrence from tumors with BMP4 granular staining was reflected in particular sites of metastasis eg, bone, liver, lung, nodes, pleura, brain, gynecological organs, GI tract, peritoneum, skin and bone marrow. In general, patients with tumors displaying BMP4 granular staining more often showed metastasis at all sites Figure 4b.

Nevertheless, no differences were statistically significant, which was likely again due to the low number of events evaluated.

BMP4 expression correlates with breast tumor recurrence. Finally, the potential association between BMP4 expression and patient survival was explored. The overall survival and breast cancer-specific survival did not differ between patients with tumors displaying granular or non-granular BMP4 staining. Since granular BMP4 staining was associated with low proliferation rate, we divided the patients further into subgroups based on the proliferation status but again found no statistically significant associations.

Time-to-event analyses were also performed for the time to first metastasis, local recurrence, first bone metastasis and disease-free time. No statistically significant differences were observed for any of the above analyses. In addition, the associations between BMP4 expression and the use of hormone-replacement therapy or BMP7 expression status were also examined, but no differences were found between tumors with granular or non-granular BMP4 staining.

BMP4 is a well-known developmental regulator that is widely expressed during early embryogenesis. Genes and signaling pathways that normally participate in developmental processes have been shown to also be reactivated in cancer pathogenesis.

Although no increase in the risk of cancer has been reported so far, these treatments are not recommended for patients with prior history of cancer. Moreover, a detailed study of BMP4 expression in a large breast cancer patient set was conducted to evaluate the clinical impact of BMP4 expression in breast cancer. It is noteworthy that the antibody used will detect both the mature BMP4 and the more stable precursor protein, and thus the protein expression data do not directly imply the activity of BMP signaling in a given tissue.

BMP4 protein expression was detected in normal and tumor tissues at variable levels. In more than one-fifth of both the benign and malignant samples, BMP4 was strongly expressed in a granular pattern possibly suggesting a presence in secretory vesicles.

BMP4 expression was more often absent in normal tissues compared with tumor tissues, while diffuse expression was more frequent in tumors. BMP4 was also commonly expressed in the epithelial cells and leukocytes within both the normal and tumor samples.

Our extensive array of normal tissues provided a comparable platform to evaluate BMP4 expression and showed that BMP4 is indeed expressed in a distinct set of adult tissues. Thus, BMP4 is likely involved in the normal physiological functions of certain adult tissues.

We found strong granular BMP4 staining in the epithelial cells of the bladder, ureter, uterine cervix and the red pulp area of the spleen for the first time. In the lung epithelium, we observed BMP4 expression patterns similar to previous findings.

Although direct comparisons between mRNA and protein expression data are not straightforward, public microarray data also demonstrate high BMP4 expression in the urogenital system, gastrointestinal organs and uterine cervix www.

The main advantage of our data compared with previous studies is that the tissue microarray format permits the identical handling of all samples, and the scoring of the data from different tissues can be performed according to comparable criteria. Notably, the previous BMP4 expression data from normal adult tissues often stemmed from studies of cancer or other diseases where the normal tissue samples were obtained as paired samples in close proximity of tumor or diseased tissue.

Nevertheless, we fully agree that the number of parallel samples in our study was low; however, their uniform staining patterns still highlights the usefulness of our data. In cancer samples, strong BMP4 expression was observed in the squamous cell carcinomas. We demonstrate for the first time strong, granular BMP4 expression in the squamous cell carcinomas of the uterine cervix, skin and lung. Our results from head and neck and esophageal squamous cell carcinomas agree with previous findings.

In colorectal and gastric cancers, BMP4 expression had been identified in the majority of the samples, but strong expression was detected only in a minority, which resembled the staining pattern we also detected.

In this study, we also show that tumor types originating from the same organ or tissue, such as those from lung or skin, can drastically differ in terms of their BMP4 expression. According to earlier reports, BMP4 protein expression was detected in a minority of a small panel of non-small cell lung carcinomas, but studies on the mRNA level of BMP4 did not indicate any differences between the subtypes of lung cancer.

Similarly to the normal tissues, comparison of our tumor protein expression data and the public mRNA expression data show a good concordance. High BMP4 mRNA expression has been commonly detected for example in lung, gastrointestinal, pancreatic, ovarian and uterine cancers whereas lower expression was seen in prostate carcinomas www.

However as stated above, such comparisons are not unproblematic and especially in the case of tumor samples, one may expect more variability in both mRNA and protein levels between different samples. Finally, the BMP4 expression patterns in the tumor samples were compared with the patterns detected in the corresponding normal tissues.

In four organs where BMP4 expression was strong in the normal tissue ie, stomach, esophagus, liver and spleen , only a subset of the tumor tissue samples expressed BMP4 at a similar level, which implies the expression of BMP4 is reduced in subset of cancers.

However, in a previous comparison of adjacent normal and tumor tissues from the stomach, liver and esophagus, BMP4 expression was higher in the tumor samples. In the case of four normal tissues ie, colon, pancreas, thyroid and ovaries where no BMP4 expression was detected, a subset of the corresponding tumor samples had strong granular BMP4 staining indicating increased BMP4 expression.

In colorectal cancer, a similar trend of increased BMP4 expression in tumor tissue has also been observed. BMP4 expression in the normal brain tissue was possibly present in the microglial cells, whereas in the tumor tissue, a similar pattern was not evident. Additionally, in the lung, the majority of the tumor samples were similarly granularly stained compared with normal lung with the exception of small cell carcinoma.

For breast cancer, this study is the first report to examine BMP4 protein expression with comprehensive patient material. The frequency of strong BMP4 expression in breast cancer was similar to the overall frequency observed in other tumor types. In the normal mammary gland tissue, BMP4 was detected only at a low level implying that strong expression is cancer specific. In our previous study, BMP4 mRNA expression was observed more often in low-grade tumors, 23 but this observation did not translate to the protein level.

However, strong BMP4 expression was more common in invasive lobular carcinomas than in ductal carcinomas. We have observed a similar expression pattern for BMP7 in the same breast cancer patient set. In our previous in-vitro functional studies, BMP4 expression decreased breast cancer cell growth and at the same time was able to increase the migration and invasion of these same cells. Previously, a low BMP4 methylation score, together with other methylation markers, correlated with a longer time to distant metastasis in breast cancer 50 ; however, we did not observe any significant changes in our time-to-event analyses.

Overall, the involvement of BMP4 in cancer progression has been studied on a very limited scale. In squamous cell carcinomas of the head and neck, strong BMP4 expression was detected particularly in tumor samples of patients with metastases and was associated with a shorter overall survival.

In conclusion, we have shown that BMP4 is expressed in a strong, granular manner in several normal tissues, which indicates that it is likely to have important functions in normal tissue homeostasis.

Variable patterns of expression were detected in multiple tumor samples with particularly strong BMP4 staining observed in squamous cell carcinomas. Most importantly, in breast cancer, strong BMP4 expression associated with low proliferation index of the tumors and an increase in tumor recurrence. These observations concur with our previous in-vitro cell line data illustrating a dualistic function for BMP4 as a growth inhibitor and promoter of migration and invasion in breast cancer.

Bone morphogenetic protein receptors and signal transduction. J Biochem ; — Article Google Scholar. Reddi AH. Bone morphogenetic proteins: an unconventional approach to isolation of first mammalian morphogens. Cytokine Growth Factor Rev ; 8 — Zhao GQ. Consequences of knocking out BMP signaling in the mouse.

Genesis ; 35 — Genes Dev ; 9 — Gene Expr Patterns ; 9 — Hogan BL. Bone morphogenetic proteins: multifunctional regulators of vertebrate development.

Genes Dev ; 10 — Robinson GW. Cooperation of signalling pathways in embryonic mammary gland development. Clinical Trials. Frederick National Laboratory for Cancer Research. Bioinformatics, Big Data, and Cancer. Annual Report to the Nation. Research Advances by Cancer Type. Stories of Discovery. Milestones in Cancer Research and Discovery. Biomedical Citizen Science.

Director's Message. Budget Proposal. Stories of Cancer Research. Driving Discovery. Highlighted Scientific Opportunities. Research Grants.

Research Funding Opportunities. Cancer Grand Challenges. Research Program Contacts. Funding Strategy. Grants Policies and Process. Introduction to Grants Process. NCI Grant Policies. Legal Requirements. Step 3: Peer Review and Funding Outcomes. Manage Your Award. Grants Management Contacts. Prior Approvals. Annual Reporting and Auditing. Transfer of a Grant. Grant Closeout. Cancer Training at NCI. Resources for Trainees. Funding for Cancer Training.